A‐T+ PET participants in preclinical AD: Clinical progression and concordance with fluid markers
Bibliographic record
Abstract
Abstract Background Amyloid‐negative tau‐positive PET (A‐T+) participants have been reported in several studies. We assessed the prevalence and characteristics of A‐T+ participants in a cohort of cognitively unimpaired individuals with a first‐degree family history of Alzheimer’s disease (AD) dementia. Method We studied 252 participants from the longitudinal PREVENT‐AD cohort (mean cognitive follow‐up = 3.42 years, SD = 2.86) who received an amyloid ( 18 F‐NAV4694) and a tau ( 18 F‐Flortaucipir) PET‐scan. The amyloid‐positivity threshold was 18 centiloids (SUVR=1.27) and tau positive threshold was set as 2SD above the mean of A‐ participants in a temporal meta‐ROI (SUVR=1.29). Follow‐up PET scans were available for 109 participants. We characterized A‐T+ participants on clinical (age, sex, APOE4 status, education, depression, apathy, anxiety, sleep), cognitive (RBANS, MMSE, ECoG) and fluid (CSF, plasma) measurements. Result In the PREVENT‐AD cohort, only 3 (1.2 %) of all studied participants were classified as A‐T+ (see Table 1 for participants characteristics). Participants 1 and 2 were positive based on plasma Aβ 42/40 and they had relatively low levels of tau binding that could represent early pathology. Participant 3 was also positive based on CSF and plasma, her Aβ‐PET scan was classified as positive on visual read and became quantitatively positive at follow‐up. Participant 3 had extensive unilateral tau binding at baseline that became bilateral at follow‐up (Figure 1). Figure 2 details the longitudinal cognitive trajectory of Participant 3. During the cognitive follow‐up, participants 1 developed mild cognitive impairment and participant 3 developed dementia. Conclusion A‐T+ individuals are rare in the PREVENT‐AD cohort and the 3 A‐T+ were classified as Aβ positive based on fluid biomarkers. One of the 3 A‐T+ individuals showed a very fast clinical progression and a tau uptake pattern atypical of AD.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".